JPS63185949A - Hydrazinosuccinic acid diester - Google Patents
Hydrazinosuccinic acid diesterInfo
- Publication number
- JPS63185949A JPS63185949A JP1688687A JP1688687A JPS63185949A JP S63185949 A JPS63185949 A JP S63185949A JP 1688687 A JP1688687 A JP 1688687A JP 1688687 A JP1688687 A JP 1688687A JP S63185949 A JPS63185949 A JP S63185949A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- hydrazinosuccinic
- acid diester
- ethanol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 Hydrazinosuccinic acid diester Chemical class 0.000 title claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 36
- 238000001816 cooling Methods 0.000 abstract description 11
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- 239000002798 polar solvent Substances 0.000 abstract description 2
- 239000003905 agrochemical Substances 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229930040373 Paraformaldehyde Natural products 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 229920002866 paraformaldehyde Polymers 0.000 description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- IEPRKVQEAMIZSS-AATRIKPKSA-N diethyl fumarate Chemical compound CCOC(=O)\C=C\C(=O)OCC IEPRKVQEAMIZSS-AATRIKPKSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RLFYROFKMULBFJ-UWTATZPHSA-N (2r)-2-hydrazinylbutanedioic acid Chemical compound NN[C@@H](C(O)=O)CC(O)=O RLFYROFKMULBFJ-UWTATZPHSA-N 0.000 description 2
- IEPRKVQEAMIZSS-UHFFFAOYSA-N Di-Et ester-Fumaric acid Natural products CCOC(=O)C=CC(=O)OCC IEPRKVQEAMIZSS-UHFFFAOYSA-N 0.000 description 2
- IEPRKVQEAMIZSS-WAYWQWQTSA-N Diethyl maleate Chemical compound CCOC(=O)\C=C/C(=O)OCC IEPRKVQEAMIZSS-WAYWQWQTSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000007259 addition reaction Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- DGKFSQSYGNVCAA-UHFFFAOYSA-N CCOC(=O)C=1C=C(O)N(C)N=1 Chemical compound CCOC(=O)C=1C=C(O)N(C)N=1 DGKFSQSYGNVCAA-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 102100034744 Cell division cycle 7-related protein kinase Human genes 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- 101000945740 Homo sapiens Cell division cycle 7-related protein kinase Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- JBSLOWBPDRZSMB-BQYQJAHWSA-N dibutyl (e)-but-2-enedioate Chemical compound CCCCOC(=O)\C=C\C(=O)OCCCC JBSLOWBPDRZSMB-BQYQJAHWSA-N 0.000 description 1
- JBSLOWBPDRZSMB-FPLPWBNLSA-N dibutyl (z)-but-2-enedioate Chemical compound CCCCOC(=O)\C=C/C(=O)OCCCC JBSLOWBPDRZSMB-FPLPWBNLSA-N 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- XZMJSBMHKVECPU-UHFFFAOYSA-N diethyl 2-hydrazinylbutanedioate Chemical compound CCOC(=O)CC(NN)C(=O)OCC XZMJSBMHKVECPU-UHFFFAOYSA-N 0.000 description 1
- VKNUORWMCINMRB-UHFFFAOYSA-N diethyl malate Chemical compound CCOC(=O)CC(O)C(=O)OCC VKNUORWMCINMRB-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、マレイン酸ジアルキルエステルあるいはフマ
ル酸ジアルキルエステルからヒドラジノスクシン酸ジエ
ステル、更にメチレンヒドラジノスクシン酸ジエステル
を経る2−メチル−3−ヒドロキシ−5−アルコキシカ
ルボニルピラゾールの製造法の一部分、即ちヒドラジノ
スクシン酸ジエステルおよびその製造法に関する発明で
ある。Detailed Description of the Invention [Industrial Application Field] The present invention relates to the production of 2-methyl-3-hydroxy hydrazinosuccinic acid diester from maleic acid dialkyl ester or fumaric acid dialkyl ester, and further to methylene hydrazinosuccinic acid diester. This invention relates to a part of the method for producing -5-alkoxycarbonylpyrazole, that is, hydrazinosuccinic acid diester and the method for producing the same.
2−メチル−3−ヒドロキシ−5−アルコキシカルボニ
ルピラゾール(I[[)は医薬、農薬の中間体として有
用であり、特に特開昭60−231679号に示された
抗高脂血症剤の中間体として有用である。2-Methyl-3-hydroxy-5-alkoxycarbonylpyrazole (I It is useful for the body.
(以下、余白)
化合物(1)はたとえばスキーム1
スキーム1
− (■)
(I[)
(反応式中の一般式中のR+、Rzは炭素数1から6の
アルキル基を意味する。)
で示されるようにオキザロ酢酸ジアルキルエステルナト
リウム塩(Vl)とメチルヒドラジンとの環化反応によ
り合成された。(Hereinafter, blank space) Compound (1) is, for example, Scheme 1 Scheme 1 - (■) (I[) (R+ and Rz in the general formula in the reaction formula mean an alkyl group having 1 to 6 carbon atoms.) As shown, it was synthesized by a cyclization reaction between oxaloacetic acid dialkyl ester sodium salt (Vl) and methylhydrazine.
しかしながら、この方法は原料となるメチルヒドラジン
が比較的高価であるという問題点を有する。However, this method has the problem that the raw material methylhydrazine is relatively expensive.
本発明者らは2−メチル−3−ヒドロキシ−5−アルコ
キシカルボニルピラゾールの新規な合成法について鋭意
検討した結果、マイレン酸ジアルキルエステルあるいは
フマル酸ジアルキルエステルからヒドラジノスクシン酸
ジアルキルエステル、更にメチレンヒドラジノスクシン
酸ジアルキルエステルを経る新規な合成法を見出し、本
発明を完成した。As a result of intensive studies on a new method for synthesizing 2-methyl-3-hydroxy-5-alkoxycarbonyl pyrazole, the present inventors found that hydrazinosuccinic acid dialkyl ester was synthesized from maleic acid dialkyl ester or fumaric acid dialkyl ester, and further, methylene hydrazinosuccinate. We discovered a new synthetic method using dialkyl succinic acid esters and completed the present invention.
以下に本発明の方法を詳細に説明する。本発明の新規合
成法を一部分の工程として含む上記新規な合成法は、下
記のスキーム2に示したようなAからDの工程から成り
、本発明の工程はAとBの工程である。(以下、余白)
スキーム2
(I)
(I[I)
〔式中、R1、R2は炭素数1から6の低級アルキル基
を意味する。〕
工程Aあるいは工程Bはフマル酸ジエステルまたはマレ
イン酸ジエステルへのヒドラジンの付加反応である。こ
の反応は水冷下あるいは室温下で進行し、また無溶媒ま
たは水、低級アルコール若しくはアセトニトリル等、各
種溶媒中またはこれらの混合溶媒中で進行するが、エタ
ノール、アセトニトリルなどの極性溶媒中ですみやかに
進行する。The method of the present invention will be explained in detail below. The above-mentioned novel synthetic method, which includes the novel synthetic method of the present invention as a part of the steps, consists of steps A to D as shown in Scheme 2 below, and the steps of the present invention are steps A and B. (Hereinafter, blank space) Scheme 2 (I) (I[I) [In the formula, R1 and R2 mean a lower alkyl group having 1 to 6 carbon atoms. ] Step A or Step B is an addition reaction of hydrazine to fumaric acid diester or maleic acid diester. This reaction proceeds under water cooling or at room temperature, and proceeds without solvent or in various solvents such as water, lower alcohols, or acetonitrile, or in a mixed solvent thereof, but it proceeds quickly in polar solvents such as ethanol and acetonitrile. do.
なおこの付加反応についてはエステルの種類により副生
成物が多く生成することがあるため、それらを防ぐため
の注意が必要である。たとえばジメチルエステル、ジエ
チルエステル、ジ−n−プロピルエステル、ジイソプロ
ピルエステル、ジ−n−ブチルエステル、ジ−S−ブチ
ルエステル、などの第1級または第2級アルコールのエ
ステルにおいては、マレイン酸ジエステルあるいはフマ
ル酸ジエステル中にヒドラジン水和物または水溶液また
は有機溶媒液を滴下すると多量のヒドラジドおよびその
他の副生成物を与える。一方例えば当モル量よりわずか
に過剰のヒドラジン水和物のアセトニトリルまたは低級
アルコール溶液中に、−5〜30°C好ましくは水冷下
でマレイン酸ジアルキルエステル、あるいはフマル酸ジ
アルキルエステルを滴下することにより副生成物の生成
を抑え、収率よく目的とする化合物(II)を得ること
が出来る。一方ジーし一ブチルエステルのごと(、化合
物(r/)あるいは化合物(V)のR+。Note that this addition reaction may produce many byproducts depending on the type of ester, so care must be taken to prevent them. For example, esters of primary or secondary alcohols such as dimethyl ester, diethyl ester, di-n-propyl ester, diisopropyl ester, di-n-butyl ester, di-S-butyl ester, maleic diester or When hydrazine hydrate or an aqueous or organic solvent solution is added dropwise to fumaric acid diester, a large amount of hydrazide and other by-products are produced. On the other hand, for example, a maleic acid dialkyl ester or a fumaric acid dialkyl ester is added dropwise to an acetonitrile or lower alcohol solution of hydrazine hydrate slightly in excess of the equimolar amount at -5 to 30°C, preferably under water cooling. The desired compound (II) can be obtained in good yield while suppressing the production of products. On the other hand, as for di-butyl ester (R+ of compound (r/) or compound (V)).
R2を共にL−ブチル基にすることにより簡単に高収率
で化合物(II)が得られる。Compound (II) can be easily obtained in high yield by replacing both R2 with L-butyl groups.
工程Cはヒドラジノスクシン酸ジエステルとホルマリン
あるいはバラホルムアルデヒドとの脱水縮合反応であり
、水、低級アルコール、テトラヒドロフラン、アセトニ
トリル等の各種溶媒中で行なうことが出来るが通常メタ
ノールあるいはエタノール中、0〜40°C好ましくは
5〜30°Cで行なわれる。またメタノール、エタノー
ルに加えてベンゼン、トルエンなどを混合し、加熱しな
から共沸脱水により反応を進行させることも出来る。Step C is a dehydration condensation reaction between hydrazinosuccinic acid diester and formalin or paraformaldehyde, and can be carried out in various solvents such as water, lower alcohols, tetrahydrofuran, acetonitrile, etc., but is usually carried out in methanol or ethanol at 0 to 40°C. C Preferably carried out at 5 to 30°C. It is also possible to mix benzene, toluene, etc. in addition to methanol and ethanol, and proceed with the reaction by azeotropic dehydration without heating.
またさらに工程Aあるいは工程Bと工程Cは連続して行
なうこともでき、その際化合物(It)は単離する必要
がない。特に、化合物(n)が反応の後処理時に変化す
ることが時に観察されており、その際この連続化は非常
に有効である。Moreover, Step A or Step B and Step C can be carried out consecutively, in which case it is not necessary to isolate the compound (It). In particular, it has sometimes been observed that the compound (n) changes during the work-up of the reaction, in which case this continuation is very effective.
工程りはメチレンヒドラジノスクシン酸ジエステル(1
)を塩基処理することにより環化′させ、目的とするピ
ラゾール誘導体(III)を得る反応であり、塩基とし
てカセイソーダ、カセイカリ、炭素数1〜5のカリウム
アルコキシドまたはナトリウムアルコキシドなどを用い
ることが出来る。また反応温度は水冷下から一5〜10
0°Cである。The process is methylene hydrazinosuccinic acid diester (1
) is cyclized by treating with a base to obtain the desired pyrazole derivative (III). Caustic soda, caustic potash, potassium alkoxide or sodium alkoxide having 1 to 5 carbon atoms, etc. can be used as the base. In addition, the reaction temperature is 15 to 10 degrees below water cooling.
It is 0°C.
この際、R1,R2がt−ブチル基の場合は特に反応が
速やかに進行し、副生成物が併なわないため、高収率を
与える。At this time, when R1 and R2 are t-butyl groups, the reaction proceeds particularly quickly and no by-products are produced, resulting in a high yield.
〔発明の効果]
以上、本発明の製造法を用いることにより、ヒドラジノ
スクシン酸第1級または第2級アルキルエステルの収率
が高くなる。[Effects of the Invention] As described above, by using the production method of the present invention, the yield of hydrazinosuccinic acid primary or secondary alkyl ester is increased.
〔実施例1]
ヒドラジノスクシン酸ジエチルエステル(I[a)
(合成例1)
80%ヒドラジン−水和物1.2g(1,1倍モル)と
アセトニトリル24m1をフラスコに入れ水冷下で撹拌
しながらジエチルマレート3gを水冷下で約30分かけ
て滴加した。水冷下で2時間撹拌した後アセトニトリル
を留去した。残渣にクロロホルムを加え水洗した。Mg
SO4で乾燥しクロロホルムを留去すると無色オイル状
のI[aが2.92 g(収率82.3%)得られた。[Example 1] Hydrazinosuccinic acid diethyl ester (I[a) (Synthesis Example 1) 1.2 g (1.1 times mole) of 80% hydrazine hydrate and 24 ml of acetonitrile were placed in a flask and stirred under water cooling. While cooling with water, 3 g of diethyl malate was added dropwise over about 30 minutes. After stirring for 2 hours under water cooling, acetonitrile was distilled off. Chloroform was added to the residue and washed with water. Mg
After drying with SO4 and distilling off the chloroform, 2.92 g (yield: 82.3%) of I[a] was obtained as a colorless oil.
(合成例2)
ジエチルマレートのかわりにジエチルフマレートを用い
実験例1と同様に処理してII a 0.85 g(収
率71.7%)を得た。(Synthesis Example 2) The same procedure as in Experimental Example 1 was carried out using diethyl fumarate instead of diethyl maleate to obtain 0.85 g (yield 71.7%) of II a.
pmrスペクトル(CDC13中)
δ(ppm) : 1.22(3H,t、 c113.
J=711z)1.25(3H,t、CI+3. J
4tlz)2.72(2H,d、 C)lz、 J=7
11z)3.55(LH,s、 Nl2)
3.78(Ill、 t、 CI、 J=7!1z)
4.11(2H1Q、C1h、 、h7Hz)4.18
(28,q、 CHz、 J=7Hz)MS(m/e)
: 205(M”+1)、204(M”)、159(
M”−0Et)。PMR spectrum (in CDC13) δ (ppm): 1.22 (3H, t, c113.
J=711z)1.25(3H,t,CI+3.J
4tlz)2.72(2H,d,C)lz, J=7
11z) 3.55 (LH, s, Nl2) 3.78 (Ill, t, CI, J=7!1z)
4.11 (2H1Q, C1h, , h7Hz) 4.18
(28,q, CHHz, J=7Hz) MS (m/e)
: 205(M"+1), 204(M"), 159(
M”-0Et).
131(M”−CO□Et)
(比較例1)
ジエチルフマレート10gをエタノール20m1に溶か
し、80%ヒドラジン水和物を3.05mji!(1,
1倍モル)水冷下、撹拌しながら滴下した。水冷下で更
に3時間撹拌した後、エタノールを室温下で留去した。131(M"-CO□Et) (Comparative Example 1) 10 g of diethyl fumarate was dissolved in 20 ml of ethanol, and 3.05 mji! (1,
(1 mole) was added dropwise while stirring under water cooling. After further stirring for 3 hours under water cooling, ethanol was distilled off at room temperature.
残渣をクロロホルムに溶解させ水洗した。硫酸マグネシ
ウムで乾燥し、クロロホルムを留去することにより、無
色オイル状の目的物を得た(見かけの収率65,9%)
。このオイル状化合物のNMRスペクトルにおいては先
に述べた化合物として同定可能なシグナルのほかに61
.86 1)11+11に二重線が観察され(J=6.
511z)、目的物のメチレンシグナルとの強度比が「
目的化合物:副生成物=2:IJであった。このシグナ
ルを与える未知化合物の構造はジエチルフマレートとヒ
ドラジンの2:l付加物と推定された。The residue was dissolved in chloroform and washed with water. By drying with magnesium sulfate and distilling off chloroform, the target product as a colorless oil was obtained (apparent yield 65.9%).
. In the NMR spectrum of this oily compound, in addition to the signals that can be identified as the compound mentioned above, 61
.. 86 1) A double line was observed at 11+11 (J=6.
511z), the intensity ratio with the methylene signal of the target object is “
Target compound: By-product = 2: IJ. The structure of the unknown compound giving this signal was estimated to be a 2:1 adduct of diethyl fumarate and hydrazine.
この副生成物の生成を考慮に入れた時の目的物の収率は
49.4%となる。When the formation of this by-product is taken into consideration, the yield of the target product is 49.4%.
(比較例2)
比較例1においてエタノールのかわりにアセトニトリル
を用いた時も同じ副生成物が生成した。(Comparative Example 2) When acetonitrile was used instead of ethanol in Comparative Example 1, the same byproducts were produced.
混合物のNMRスペクトルから計算した目的物と副生成
物の比は4:1であった。それを考慮した時の目的物の
収率は65.2%となる。The ratio of the target product to the by-product calculated from the NMR spectrum of the mixture was 4:1. Taking this into consideration, the yield of the target product is 65.2%.
〔実施例2〕
ヒドラジノスクシン酸ジ−n−ブチルエステル(Ilc
)
ジエチルマレートのかわりにジ−n−ブチルマレートを
用い参考例1の合成例1と同様にして目的物を得た。無
色油状物(収率95%)pmrスペクトル(CDCh中
)
δ(ppm): 0.92(6H,m、 CI+3X2
)。[Example 2] Hydrazinosuccinic acid di-n-butyl ester (Ilc
) The desired product was obtained in the same manner as in Synthesis Example 1 of Reference Example 1 using di-n-butyl maleate instead of diethyl maleate. Colorless oil (yield 95%) PMR spectrum (in CDCh) δ (ppm): 0.92 (6H, m, CI+3X2
).
1.15〜1.95(8H,m、 CH2C)12X2
)。1.15-1.95 (8H, m, CH2C) 12X2
).
2.70(2H,d、 CHz、J=6Hz) 。2.70 (2H, d, CHHz, J=6Hz).
3.50(2H,s、 NHz) 。3.50 (2H, s, NHz).
3.76(IH,t、 C)l、 J=6)Iz) 。3.76 (IH, t, C)l, J=6)Iz).
4.05(2H,t、 QC)Iz、 J=6Hz)1
4.11(2tl、 t、 0Ct(z、 J=611
z)〔参考例1〕
ヒドラジノスクシン酸ジーも一ブチルエステル(nb)
ジーし一ブチルフマレート20gをエタノール120m
1に溶かし、室温でヒドラジン−水和物(80%) 6
.6 m(1(1,38倍モル)を加えた。4.05 (2H, t, QC)Iz, J=6Hz)1
4.11(2tl, t, 0Ct(z, J=611
z) [Reference Example 1] Hydrazinosuccinic acid di-butyl ester (nb) Di-butyl fumarate (20 g) was dissolved in 120 m of ethanol.
Hydrazine hydrate (80%) dissolved in 1 and 6 at room temperature.
.. 6 m (1 (1.38 times mole)) was added.
室温で5時間撹拌した後低温でエタノールを留去した。After stirring at room temperature for 5 hours, ethanol was distilled off at low temperature.
クロロホルムを加え水洗しクロロホルム層をMg5On
で乾燥した後溶媒を留去すると無色オイル状のnbが2
2.4g(収率98.0%)得られた。Add chloroform, wash with water, and convert the chloroform layer to Mg5On.
When the solvent is distilled off after drying with
2.4 g (yield 98.0%) was obtained.
pmrスペクトル(CDC7! 、中)δ(ppm):
1.44(9H,s、 t−Bu)。PMR spectrum (CDC7!, medium) δ (ppm):
1.44 (9H,s, t-Bu).
1.46(9)1. s、 t−Bu)。1.46(9)1. s, t-Bu).
2.61(2H,d、 CHz、 J=6Hz)。2.61 (2H, d, CHHz, J=6Hz).
3.59(IH,t、 CH,J=6)1z)。3.59 (IH, t, CH, J=6)1z).
4.10(3H,m、 NHNHz)
MS(m/e): 188(M”−’BuQH)〔参考
例2〕
メチレンヒドラジノスクシン酸ジエチルエステル(I
a)
化合物(na)9.43g、ベンゼン60 ml、エタ
ノール20IIIl及びパラホルムアルデヒド1.39
g(化合物(na)に対し1倍モル当量)をフラスコに
入れオイルバス上でかきまぜながら85°に加熱、共沸
脱水により水を留去した。薄層クロマトグラフィーで化
合物(Ia)の消失をチェックしながらパラホルムアル
デヒドを0.1 倍モル当量ずつ追加した。化合物(I
a)のスポットが消失したら加熱をやめ、溶媒を留去
し、クロロホルムを加え、アルカリ水で2回洗浄した。4.10 (3H, m, NHNHz) MS (m/e): 188 (M''-'BuQH) [Reference Example 2] Methylenehydrazinosuccinic acid diethyl ester (I
a) Compound (na) 9.43 g, benzene 60 ml, ethanol 20 III and paraformaldehyde 1.39
g (1-fold molar equivalent relative to compound (na)) was placed in a flask, heated to 85° while stirring on an oil bath, and water was distilled off by azeotropic dehydration. Paraformaldehyde was added in 0.1 molar equivalents while checking the disappearance of compound (Ia) by thin layer chromatography. Compound (I
When the spot a) disappeared, heating was stopped, the solvent was distilled off, chloroform was added, and the mixture was washed twice with alkaline water.
無水硫酸マグネシウムで乾燥し、クロロホルムを留去す
ると無色オイル状の化合物(Ia)が8.63g(収率
86.5%)得られた。After drying over anhydrous magnesium sulfate and distilling off chloroform, 8.63 g (yield 86.5%) of Compound (Ia) was obtained as a colorless oil.
pmrスペクトル(CDCI 、中)
δ(ppm): 1.28(68,t、 C1,、J=
7Hz)。pmr spectrum (CDCI, medium) δ (ppm): 1.28 (68, t, C1,, J=
7Hz).
2.85(2tl、 d、 CHz、 J=6Hz)
。2.85 (2tl, d, CHHz, J=6Hz)
.
4.15(2L q、 Ctlz、 J=711z)
。4.15 (2L q, Ctlz, J=711z)
.
4.20(2H,q、 C)Iz、J□7Hz) 。4.20 (2H, q, C) Iz, J□7Hz).
(注)メチンプロトンのシグナルがこ の領域に重複。(Note) This is the signal of the methine proton. overlap in the area.
5.95(LH,s、 NH)。5.95 (LH, s, NH).
[参考例3]
メチレンヒドラジノ−スクシン酸ジーも一ブチルエステ
ル(I b)
(合成例1)
化合物(Ilb)22gをメタノール120m!!に溶
かし、パラホルムアルデヒド5.08g(2倍モル)を
粉末のまま室温で少量ずつ加えた。室温で4時間撹拌し
た後、パラホルムアルデヒドを濾別し低温でメタノール
を留去した。残渣にエーテルを加えアルカリ水で洗浄し
た。エーテル層をMgSO4で乾燥しエーテルを留去す
ると無色オイル状のIbが21.0g(収率91.1%
)得られた。[Reference Example 3] Methylenehydrazino-succinic acid di-butyl ester (Ib) (Synthesis Example 1) 22g of compound (Ilb) was mixed with 120ml of methanol! ! 5.08 g (2 times the mole) of paraformaldehyde was added in powder form little by little at room temperature. After stirring at room temperature for 4 hours, paraformaldehyde was filtered off, and methanol was distilled off at low temperature. Ether was added to the residue and washed with alkaline water. The ether layer was dried with MgSO4 and the ether was distilled off, yielding 21.0 g of Ib as a colorless oil (yield 91.1%).
) obtained.
(合成例2)
ジーし一ブチルマレート10gをエタノール20m1に
溶かしヒドラジン−水和物(80%)を3.05 ml
(1,1倍モル)室温で滴加した。室温で2時間撹拌
した後、パラホルムアルデヒド1゜32g(1倍モル)
とベンゼン50m!!を加え85°Cで45分共沸脱水
した。溶媒を留去しエーテルを加えアルカリ水で3回洗
浄した。エーテル層をMgSO4で乾燥し、溶媒を留去
すると無色オイル状の化合物(lb )が11.77
g (収率98.6%)得られた。(Synthesis Example 2) Dissolve 10 g of di-butyl malate in 20 ml of ethanol and add 3.05 ml of hydrazine hydrate (80%).
(1.1 times mole) was added dropwise at room temperature. After stirring at room temperature for 2 hours, 1.32 g (1 mole) of paraformaldehyde was added.
And benzene 50m! ! was added and azeotropically dehydrated at 85°C for 45 minutes. The solvent was distilled off, ether was added, and the mixture was washed three times with alkaline water. The ether layer was dried with MgSO4 and the solvent was distilled off, yielding a colorless oily compound (11.77 lb).
g (yield 98.6%) was obtained.
pmrスペクトル(CDCl 3中)
δ (ppm): 1.イ3(1811,s、 t
−Bu)。PMR spectrum (in CDCl 3) δ (ppm): 1. I3 (1811, s, t
-Bu).
2.74(2)1. d、 CI+2. J=611z
) 。2.74(2)1. d, CI+2. J=611z
).
4.15(Ill、 m、 CIり。4.15 (Ill, m, CI r.
5.90(ill、 s、 NH)。5.90 (ill, s, NH).
6.15.6.70(2H,d、 ’N=Cl1z、
J=1211z)〔参考例4〕
メチレンヒドラジノ−スクシン酸ジ−n−ブチエステル
(Uc)
実施例1において化合物(Ila)のかわりに化合物(
I[c)を用い実施例1と同様にして目的物を得た。収
率90% 無色油状物
pmrスペクトル(CDC(13中)
δ(ppm): 0.94(6tl、 m、 Cll3
X2)。6.15.6.70 (2H, d, 'N=Cl1z,
J=1211z) [Reference Example 4] Methylenehydrazino-succinic acid di-n-butyester (Uc) In Example 1, compound (Ila) was replaced with compound (
The desired product was obtained in the same manner as in Example 1 using I[c). Yield 90% Colorless oil PMR spectrum (CDC (in 13) δ (ppm): 0.94 (6 tl, m, Cll3
X2).
1.15 〜1.95(8B、 m、 CH2CH
2X2)。1.15 ~ 1.95 (8B, m, CH2CH
2X2).
2.87(2H,d、 C12,J=611z)。2.87 (2H, d, C12, J=611z).
4.08(2H,t、 0C1h、 J=6)1z
)。4.08 (2H, t, 0C1h, J=6)1z
).
4.13(2H,t+ 0CIlz、 J=6Hz
) 。4.13 (2H, t+ 0CIlz, J=6Hz
).
4.38(IH,t+ CH,J=6Hz)。4.38 (IH, t+ CH, J=6Hz).
6、16(III、 d、 N=CH2,J=12
11Z) 。6, 16 (III, d, N=CH2, J=12
11Z).
6.70(ill、 d、 N=CIh、 J工
12Hz) 。6.70 (ill, d, N=CIh, J engineering 12Hz).
〔参考例5〕 。[Reference example 5].
2−メチル−3−ヒドロキシ−5−エトキシカルボニル
ピラゾール(Illa)
化合物(Ia)Igをエタノール5 mlに熔かし、ナ
トリウム0.12g(1,1倍モル)をエタノール15
m1に溶かした溶液を水冷下で滴加した。水冷下で5時
間撹拌した後エタノールを低温で留去し残渣に少量の水
を加えて溶かした。水溶液をクロロホルム洗浄すること
により不純物を除いた。水溶液に稀塩酸を加えp)II
とし、化合物(■a)をクロロホルムに抽出した。クロ
ロホルム層をMgSO4で乾燥し、溶媒を留去すると薄
茶色の固体状の化合物(nla )が0.40g(収率
51.2%)得られた。2-Methyl-3-hydroxy-5-ethoxycarbonylpyrazole (Illa) Compound (Ia) Ig was dissolved in 5 ml of ethanol, and 0.12 g (1.1 times mole) of sodium was dissolved in 15 ml of ethanol.
A solution dissolved in ml was added dropwise under water cooling. After stirring for 5 hours under water cooling, ethanol was distilled off at low temperature, and a small amount of water was added to the residue to dissolve it. Impurities were removed by washing the aqueous solution with chloroform. Add dilute hydrochloric acid to the aqueous solution p) II
Then, compound (■a) was extracted into chloroform. The chloroform layer was dried with MgSO4 and the solvent was distilled off to obtain 0.40 g (yield 51.2%) of a light brown solid compound (nla).
pmrスペクトル(CDCl 、中)
δ(ppm) : 1.30(3H,t、 C113,
J=7112) 。pmr spectrum (CDCl, medium) δ (ppm): 1.30 (3H, t, C113,
J=7112).
3.70(3H,s、 N−C1h)。3.70 (3H, s, N-C1h).
4.32(2H1q、CH2,、b711z) 。4.32 (2H1q, CH2,, b711z).
ノII
5.97(ill、 s、−\ )
MS(m/e): 170(M”)、 142(M”−
C2)1s)。No II 5.97 (ill, s, -\) MS (m/e): 170 (M"), 142 (M"-
C2) 1s).
124(?l”−EtOH)、 98(M”−)1cO
□Et)〔参考例6〕
2−メチル−3−ヒドロキシ−5−t−ブトキシカルボ
ニルピラゾール(I[[b)
化合物(Ib)9.2gをエタノール40mjl!に溶
かしナトリウム0.93g(1,2倍モル)をエタノー
ル50mj!に溶かした溶液を室温で滴下した。室温で
2.5時間撹拌した後エタノールを留去した。残渣に
水を加えクロロホルム洗浄し不純物ヲ除いた。水層から
pi(3でクロロホルム抽出した。クロロホルム層をM
g5Onで乾燥した後溶媒を留去するとガラス状の淡黄
色の化合物(IITb )が5゜12g(収率76.5
%)得られた。124(?l”-EtOH), 98(M”-)1cO
□Et) [Reference Example 6] 2-Methyl-3-hydroxy-5-t-butoxycarbonylpyrazole (I [[b) 9.2 g of compound (Ib) was added to 40 mjl of ethanol! Dissolve 0.93 g (1.2 times the mole) of sodium in 50 mj of ethanol! was added dropwise at room temperature. After stirring at room temperature for 2.5 hours, ethanol was distilled off. Water was added to the residue and washed with chloroform to remove impurities. The aqueous layer was extracted with chloroform using pi (3).The chloroform layer was extracted with M
After drying with g5On and distilling off the solvent, 5.12 g of a glassy pale yellow compound (IITb) was obtained (yield 76.5
%) obtained.
pmrスペクトル(CDCA 、中)
δ(ppm): 1.50(9tl、 s、 t−B
u)。pmr spectrum (CDCA, medium) δ (ppm): 1.50 (9tl, s, t-B
u).
3.63(3H,s、 N−CHz)。3.63 (3H, s, N-CHz).
MS(m/e): 198(M”)、 142(M”−
t−Bu)。MS (m/e): 198 (M"), 142 (M"-
t-Bu).
125(M”−0Bu’)125 (M"-0Bu')
Claims (2)
基を意味する。〕により表わされるヒドラジノスクシン
酸ジエステル。(1) General formula (II) ▲There are numerical formulas, chemical formulas, tables, etc.▼ (II) [In the formula, R^1 and R^2 mean an alkyl group having 1 to 6 carbon atoms. hydrazinosuccinic acid diester represented by ].
たは第2級のアルキル基を意味する。〕により表わされ
る化合物または一般式(VI) ▲数式、化学式、表等があります▼(VI) 〔式中、R^1、R^2は、上述の説明と同意味である
。〕により表わされる化合物を滴下させることにより生
成する一般式(II) ▲数式、化学式、表等があります▼(II) 〔式中、R^1、R^2は、上述の説明と同意味である
。〕により表わされるヒドラジノスクシン酸ジエステル
の製法。(2) General formula (V) in hydrazine solution ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (V) [In the formula, R^1 and R^2 are primary or secondary carbon atoms of 1 to 6 means an alkyl group. ] Compound or general formula (VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VI) [In the formula, R^1 and R^2 have the same meanings as in the above explanation. ] General formula (II) produced by dropping a compound represented by ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) [In the formula, R^1 and R^2 have the same meaning as the above explanation. be. ] A method for producing hydrazinosuccinic acid diester represented by
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1688687A JPS63185949A (en) | 1987-01-27 | 1987-01-27 | Hydrazinosuccinic acid diester |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1688687A JPS63185949A (en) | 1987-01-27 | 1987-01-27 | Hydrazinosuccinic acid diester |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63185949A true JPS63185949A (en) | 1988-08-01 |
Family
ID=11928652
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1688687A Pending JPS63185949A (en) | 1987-01-27 | 1987-01-27 | Hydrazinosuccinic acid diester |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS63185949A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003513207A (en) * | 1999-10-26 | 2003-04-08 | ツェットエフ レムフェルダー メタルヴァーレン アクチエンゲゼルシャフト | Shifting device for electronically controlled vehicle automatic transmission |
-
1987
- 1987-01-27 JP JP1688687A patent/JPS63185949A/en active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003513207A (en) * | 1999-10-26 | 2003-04-08 | ツェットエフ レムフェルダー メタルヴァーレン アクチエンゲゼルシャフト | Shifting device for electronically controlled vehicle automatic transmission |
JP4732653B2 (en) * | 1999-10-26 | 2011-07-27 | ツェットエフ レムフェルダー ゲゼルシャフト ミット ベシュレンクテル ハフツング | Shift device for electronically controlled vehicle automatic transmission |
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